PMID- 15099024
OWN - NLM
STAT- MEDLINE
DCOM- 20040512
LR  - 20190513
IS  - 0022-3069 (Print)
IS  - 0022-3069 (Linking)
VI  - 63
IP  - 4
DP  - 2004 Apr
TI  - Activation of matrix metalloproteinase-3 and agrin cleavage in cerebral 
      ischemia/reperfusion.
PG  - 338-49
AB  - Matrix metalloproteinase-3 (MMP-3) degrades components of the extracellular 
      matrix and may participate in the pathogenesis of stroke. Here we examine the 
      expression, activation, and cellular location of MMP-3 and the cleavage of agrin, 
      an MMP-3 substrate, following transient middle cerebral artery occlusion in the 
      rat. MMP-3 was activated by ischemia/reperfusion, which was revealed by the 
      appearance of a cleaved form and increased degradation of a substrate. MMP-3 was 
      observed in ischemic neurons, oligodendrocytes, microvasculature, and reactive 
      microglia/macrophages. In cell cultures, MMP-3 expression was observed in neurons 
      and, to a lesser extent, in mature oligodendrocytes, but not in oligodendrocyte 
      progenitors, astrocytes, or microglia. Casein zymography revealed MMP-3 in 
      cultured neurons. Agrin was expressed in cultured neurons and cultured 
      astrocytes. In brain tissue, agrin was detected in neurons, and following 
      ischemia it was also detected in reactive astrocytes. Addition of MMP-3 to 
      protein extracts from control brain caused neuronal agrin degradation. Following 
      ischemia/reperfusion, agrin disappeared from the tissue membrane fraction and a 
      cleaved agrin fragment was found in tissue protein extracts. The present results 
      show MMP-3 activation and neuronal transmembrane agrin cleavage after 
      ischemia/reperfusion. In addition, the finding that MMP-3 cleaves brain agrin 
      strongly suggests that ischemia-induced MMP-3 activation causes agrin cleavage.
FAU - Sole, Sonia
AU  - Sole S
AD  - Departament de Farmacologia i Toxicologia, IIBB-CSIC, Institut d'Investigacions 
      Biomediques August Pi i Sunyer, Barcelona, Spain.
FAU - Petegnief, Valerie
AU  - Petegnief V
FAU - Gorina, Roser
AU  - Gorina R
FAU - Chamorro, Angel
AU  - Chamorro A
FAU - Planas, Anna M
AU  - Planas AM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - 0 (Agrin)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Agrin/*metabolism
MH  - Animals
MH  - Astrocytes/metabolism
MH  - Blotting, Western
MH  - Brain Ischemia/*metabolism/physiopathology
MH  - Cells, Cultured
MH  - Enzyme Activation/*physiology
MH  - Immunohistochemistry
MH  - Male
MH  - Matrix Metalloproteinase 3/*metabolism
MH  - Microglia/metabolism
MH  - Neurons/metabolism
MH  - Oligodendroglia/metabolism
MH  - Rats
MH  - Reperfusion Injury/*metabolism/physiopathology
EDAT- 2004/04/22 05:00
MHDA- 2004/05/13 05:00
CRDT- 2004/04/22 05:00
PHST- 2004/04/22 05:00 [pubmed]
PHST- 2004/05/13 05:00 [medline]
PHST- 2004/04/22 05:00 [entrez]
AID - 10.1093/jnen/63.4.338 [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 2004 Apr;63(4):338-49. doi: 10.1093/jnen/63.4.338.